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Kevin Eric Smith ,
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Occurrence of gout in rheumatoid arthritis: it does happen! A population-based study





Aim



It has been a popular belief that gout does not typically occur in patients with rheumatoid arthritis (RA). Our aim was to assess the occurrence, prevalence, clinical presentation and possible risk factors for gout in patients with RA.



Patients & methods



We retrospectively reviewed a population-based incidence cohort of patients who fulfilled 1987 ACR criteria for RA between 1980 and 2007. The cumulative prevalence of gout in RA adjusted for the competing risk of death was estimated.



Executive summary



Background



  • ■ The coexistence of gout and rheumatoid arthritis (RA) is only rarely reported.
  • ■ Our aim was to assess the occurrence, prevalence and risk factors for gout in RA in a population-based cohort.




Patients & methods



  • ■ We retrospectively reviewed a population-based incidence cohort of patients who fulfilled 1987 ACR criteria for RA between 1980 and 2007.
  • ■ Gout was defined using the physician diagnosis along with typical monosodium urate crystal positivity in synovial fluid or the 1977 American Rheumatism Association clinical criteria for gout.
  • ■ Cumulative prevalence of gout in RA adjusted for the competing risk of death was estimated. Cox models were used to assess risk factors for gout in RA.


Results



  • ■ The 25-year cumulative incidence of gout in RA was 2.4%.
  • ■ On 1 January 2008, the prevalence of gout in this population-based cohort of patients with RA was 1.9%.
  • ■ The risk factors for gout in RA were found to be older age, male sex and obesity.


Discussion



  • ■ The prevalence of gout in patients with RA was significantly lower than the expected age- and sex-specific prevalence rate from the general population.
  • ■ The development of gout occurred more frequently in patients with RA diagnosed in recent years (1995-2007) than among patients with RA diagnosed in earlier years (1980-1994).
  • ■ The reasons for the increased incidence in patients diagnosed with RA in recent years may be owing to an increase in the incidence of risk factors for gout, such as obesity, hypertension and chronic kidney disease, in recent decades.
  • ■ In our study, age, male sex and obesity were identified as risk factors for gout in patients with RA, which are risk factors for gout identified in the general population.
  • ■ Contrary to popular belief, gout does occur in patients with RA, although at a lower rate. This finding stresses the importance of synovial fluid analysis for crystals or dual-energy computed tomography imaging in suspicious cases of coexistent RA and gout.


Results



The cohort included 813 patients with incident RA between 1 January 1980 and 31 December 2007. The characteristics of the 813 patients are listed in Table 1. All patients were 18 years or older; there were 556 women (68%) and 257 men (32%). The mean age at diagnosis of RA was 55.9 years. The average length of follow-up was 9.6 years with 9771 total person-years. Rheumatoid factor was positive in 537 (66%) patients. A total of 627 (77%) patients had received corticosteroids, 737 (91%) had taken an NSAID for the treatment of RA sometime during their disease course and 349 (43%) used low-dose aspirin daily.



Table 1



Characteristics of 813 patients with rheumatoid arthritis included in the study.



Characteristics at rheumatoid arthritis incidenceValue
Age (years), mean (+_SD)55.9 (+_15.7)
Female, n (%)556 (68)
Length of follow-up (total person-years: 9771; years), mean (+_SD)12.0 (+_7.2)
ESR at index (mm/h), mean (+_SD)24.8 (+_20.5)
Highest ESR in first year (mm/h), mean (+_SD)32.7 (+_25.7)
Rheumatoid factor positive, n (%)537 (66)
Severe extra-articular features (anytime), n (%)90 (11)
Current smoker, n (%)178 (22)
Former smoker, n (%)271 (33)
Medication use anytime during follow-up
Corticosteroid use, n (%)627 (77)
NSAID use, n (%)737 (91)
Daily low-dose aspirin use, n (%)349 (43)




Defined according to Malmo criteria [15].





Out of the 813 patients with RA, 22 patients had coexisting gout and RA. The characteristics of these 22 patients are listed in Table 2. Mean age at the time of gout diagnosis was 69.6 years. Mean BMI of these patients was 33.4 kg/m2. Rheumatoid factor and/or anticitrullinated protein was present in 14 out of 22 patients (64%). The mean uric acid level at the onset of gout was 8.2 mg/dl (normal reference ranges: male 4.3-8.0; female 2.7-6.1 mg/dl; information available for 17 out of 22 patients). The mean creatinine level at the onset of gout was 1.4 mg/dl (normal reference ranges: male 0.8-1.3; female 0.8-1.1 mg/dl; information available for 18 out of 22 patients). Diuretic use at onset of gout included nine (41%) out of 22 patients on thiazides and seven (32%) patients on furosemide. Recurrent attacks of gout were present in nine (41%) out of 22 patients and one (4%) out of 22 patients had a documented clinical history of tophi. The metatarsal phalangeal joint was involved in 12 (55%) cases, and urate crystals were identified in synovial fluid in nine (41%) patients.



Table 2



Characteristics of 22 patients with coexisting gout and rheumatoid arthritis.



Characteristics at gout diagnosisValue
Age (years), mean (+_SD)69.6 (+_10.4)
Female sex, n (%)12 (54)
BMI (kg/m2), mean (±SD)33.4 (+_9.1)
Rheumatoid factor and/or ACPA positivity, n (%)14 (64)
Uric acid (n = 17; mg/dl), mean (+_SD)8.2 (+_2.3)
Creatinine (n = 18; mg/dl), mean (+_SD)1.4 (+_0.5)
History of thiazide use, n (%)9 (41)
History of furosemide use, n (%)7 (32)
History of recurrent attacks of gout, n (%)9 (41)
Involvement of metatarsal phalangeal joint, n (%)12 (54)
Tophi, n (%)1 (4)
Identification of urate crystals, n (%)9 (41)




ACPA: Anticitrullinated protein antibody; SD: Standard deviation.



Out of the 22 patients with coexistent gout and RA, six had gout prior to RA incidence date. Including these six with prevalent gout, the 25-year cumulative prevalence of gout diagnosed by clinical criteria in this cohort of patients with RA was 5.3% (95% CI: 2.0-8.6%) (Figure 1). Excluding the six with prevalent gout, the 25-year cumulative incidence of gout was 2.4% (95% CI: 1.1-3.6%). Including only the nine patients with crystal-proven gout attacks following RA incidence, the minimum 25-year cumulative incidence of gout diagnosed by clinical criteria was 1.3% (95% CI: 0.3-2.3%).





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Figure 1



Cumulative prevalence of gout among 813 patients with rheumatoid arthritis



RA: Rheumatoid arthritis.



Acknowledgments



This work was supported by a grant from the NIH, NIAMS (R01 AR46849), the Rochester Epidemiology Project (R01 AG034676 from the National Institute on Aging) and Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS).









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